脂联素 2 连接炎症和粘连在炎症性肠病（IBD）和强直性脊柱炎（AS）的临床重叠。
Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS).
机构信息
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.
出版信息
Arthritis Res Ther. 2020 Mar 18;22(1):51. doi: 10.1186/s13075-020-02149-4.
BACKGROUND
Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis.
METHODS
Baseline colonic pathology was conducted in the ank/ank mouse model. Serum lipocalin 2 was analyzed by ELISA, in ank/ank mutants versus C3FeB6-A/Awt/wt, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the ank/ank mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) was examined by real-time PCR. Intraperitoneal injection was done with the PPARγ agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day.
RESULTS
This study showed that the ank/ank mice with fully fused spines had concurrent colonic inflammation. By first using the ank/ank mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the ank/ank mouse model involving PPARγ. Colonic expression of PPARγ was negatively associated with the degree of gut inflammation. The PPARγ agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPARγ in the aberrant expression of lipocalin 2.
CONCLUSIONS
In summary, lipocalin 2 modulated by PPARγ could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.
背景
肠道炎症和关节强直之间的临床重叠的机制知之甚少，例如炎症性肠病（IBD）和强直性脊柱炎（AS）的同时发生。由于菌群失调可能是一个共同的致病因素，具有多种抗菌作用的多效因子脂联素 2 可能是一种潜在的介质，因为它在炎症和骨稳态中发挥作用。
方法
在 ank/ank 小鼠模型中进行基线结肠病理学检查。通过 ELISA 分析 ank/ank 突变体与 C3FeB6-A/Awt/wt、同时患有 AS-IBD、AS 单独、IBD 单独或机械性背痛的患者以及健康对照者的血清脂联素 2。在 ank/ank 小鼠模型中，通过实时 PCR 检查核受体过氧化物酶体增殖物激活受体 γ（PPARγ）的表达。连续四天进行腹腔注射 PPARγ 激动剂罗格列酮或拮抗剂双酚 A 二缩水甘油醚。第六天检查血清脂联素 2 水平。
结果
本研究表明，脊柱完全融合的 ank/ank 小鼠同时伴有结肠炎症。通过首先使用具有进行性强直和亚临床结肠炎的 ank/ank 小鼠模型，在同时患有 AS 和 IBD 的患者中得到证实，循环脂联素 2 水平升高与同时存在的强直和肠道炎症有关。进一步使用涉及 PPARγ 的 ank/ank 小鼠模型研究脂联素 2 的细胞内途径。PPARγ 的结肠表达与肠道炎症的严重程度呈负相关。PPARγ 激动剂罗格列酮治疗显著上调血清脂联素 2 水平，表明 PPARγ 可能在脂联素 2 的异常表达中起调节作用。
结论
总之，PPARγ 调节的脂联素 2 可能是 AS 和 IBD 中同时存在的炎症和强直的潜在途径。
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